Discrete populations of stem cells reside within placental tissue (amnion, chorion, and umbilical cord matrix). Because of the ease of collection, and the abundance of placental tissue harvested after birth, there is a growing interest in using these stem cells for tissue regenerative medicine purposes. Placental stem cells, have multi-lineage potential beyond that of adult, bone marrow-derived mesenchymal stem cells (MSC), with the ability to differentiate to all three germ layers (ectoderm, endoderm, and mesoderm) in vivo. Amnion, chorion, and umbilical cord matrix stem cells (UCM-SCs) all demonstrate immunosuppressive effects similar to bone marrow derived MSC, indicating that allogeneic transplantation of these cells for regenerative therapies may be possible. In fact, allogeneic bone marrow-derived MSC are currently being evaluated as a therapeutic for steroid refractory graft versus host disease in Phase III studies, providing a precedent for the use of allogeneic stem cells in a clinical setting. The tissue regenerative capacity of placental stem cells, however, remains unclear. Furthermore, the utility of banked allogeneic placental stem cells for skeletal tissue repair has not yet been tested. In this proposal, we will examine the skeletal regenerative potential of autologous and allogeneic placental stem cells. In collaboration with the UC Davis Center for Equine Health and UC Davis, we will use horses as a non-terminal, large animal model to explore the feasibility of banking autologous and allogeneic equine placental stem cells for musculoskeletal regenerative medicine applications. The equine studies described in this narrative provide a unique opportunity to bring novel cell based therapies to the veterinary market, while also modeling allogeneic placental stem cells as a treatment for orthopedic injuries in humans. PUBLIC HEALTH RELEVANCE: Adult mesenchymal stem cells hold great promise for treating a multitude of diseases and injuries, including limb ischemia associated with diabetes, chronic skin ulcers, and bone fractures. In this proposal, we will examine the therapeutic potential of allogeneic umbilical cord matrix stem cells isolated from placental tissue. We believe that these primitive stem cells, harvested from tissue at birth and banked for later therapeutic applications, hold even greater tissue repair and regeneration potential than adult derived cells. Our studies will define the therapeutic potential of these cells and help bring novel stem cell therapies to the clinic.